Tag Archives: ALK mutation

ABC World News November 10th, 2009: some questions and answers about PF-02341066

On Tuesday night, November 10th, ABC World News aired a story that was a follow-up to their June 2nd, 2009 report on personalized cancer care. Tuesday’s report featured Bill Shuette, the gentleman I had the pleasure of meeting last week. Click here to see the report.  When the story about my response to PF-02341066 aired in June, there was a flurry of interest in this new “wonder” drug. Many people were disappointed that this treatment was not the answer for them or their loved ones. However, for a handful of people, it was indeed a lifesaver. Bill is among them.

Once again, message boards are heating up with interest, and I would presume that MGH and other facilities that are  sponsoring the third phase of the PF-02341066 trial will field many phone calls.  As the ALK mutation occurs in a minority of lung cancer patients (3-7% of lung cancers, adjusted up to c. 13% for light to never-smokers), this treatment will not be appropriate for the majority. However, I have no doubt it will prove a godsend to some.

Traffic on my blog was much heavier yesterday, with many people logging on to read about PF-02341066.  As I have been on trial for more than 13 months now, I am in a somewhat unique position to provide the perspective of a trial participant, or subject.  This is, of course, not to be confused with medical advice which I am not qualified to give.  What I can do though, is tell you about my own experience with this drug.  Let’s pretend I am being interviewed:

How is the drug administered?

The drug is in capsule form.  At this stage of the trial, 250mg twice a day is the standard dosage, as it was when I entered the trial.  I take three gray capsules in the morning, and three more at night.

The first time you took the pills, what did it feel like?

I felt a little woozy; just a bit different or altered.  I had severe diarrhea within an hour, as well as mild nausea.  The diarrhea cleared up after several episodes that day, as well as administration of some immodium, and it was not an issue again. I felt somewhat fatigued as well.

Were there potentially more severe side effects as well?

My heart rate was monitored very closely initially, and at one point I had a questionable EKG (mild arrhythmia).  It happened once and and proved to be a non issue.  There was also the potential for liver inflammation, and my liver enzymes rose sharply after a few weeks.  They never reached a dangerous level of concentration, and quickly began to decrease before settling at a slightly elevated level where they remain.  It is interesting to note that when I had to take a holiday from the drug during surgery for my ankle, my enzymes dropped to a level that was very close to normal. Perhaps a week after the onset of regular dosing, I awoke with a very noticeable visual disturbance:  it was as if everything had a light trail or ghost image.  This effect was most noticeable in low light conditions, and/or when I was transitioning from dark to light.  I would eventually learn that this is a condition called palinopsia and is a side effect of certain drugs.

What were the positive effects and how quickly did you notice them?

When I started the trial, I was coughing almost constantly and was noticeably short of breath.  When I lay down at night my lungs “rattled” in a way that was all too familiar:  I knew it was the cancer.  I could tell that my immune system was depressed in general, as I had begun to have secondary infections and to feel crummy all the time.  It was obvious to me that I was dying, and it was scary as hell.

The first dose of PF-02341066 was a lead-in dose.  This meant that a whole week passed before I began daily dosing.  Within days of taking the full dose, all of the above symptoms began to fade.  It was truly amazing.  By two weeks, I had no cough and I could breathe so much more freely.

Were there lingering negative side effects?

Nausea hasn’t been a big issue for me, but I do have days where I am queasy and on two occasions I have vomited.  In the beginning, as a variation on the trial, we were not allowed to eat for several hours before and after taking the capsules, and the nausea was much more bothersome.  Taking the drug on a full stomach definitely helps.  For perhaps the first eight months, I would seem to hit a wall of fatigue at about 8 pm.  I have noticed that exercising actually makes this fatigue far less noticeable, and I can stay up until 9 pm now–even stretching it to 10 some nights.  I definitely require more sleep than I once did; perhaps averaging ten hours a night.  After a few months, I became aware that the peripheral neuropathy in my feet and hands (a lingering result of chemotherapy) was more noticeable again.  I am no longer so aware of it.  The palinopsia, or visual disturbance is not so noticeable either, although driving at night is more challenging than it once was.  I am unsure as to whether or not these side effects have actually lessened, or if my brain has simply adjusted to a new reality.

After several months of being on trial, I had a very sharp pain in my chest upon swallowing and I coughed up a small amount of blood.  After questioning me about my symptoms, Dr. Shaw felt that it was esophageal in origin.  A look down my throat with a scope confirmed the presence of an esophageal ulcer; likely as a result of an incompletely swallowed capsule.  It was quickly resolved with several doses of Carafate.  I now make sure to drink lots of water with my pills and I usually take a bite of something as well (such as applesauce) to make sure they all went down.

One interesting, if benign, side effect has been a sharply increased sense of smell. I can smell everything now with such acuity, that I feel kind of like a bloodhound.   There are situations where this is not a good thing, but for the most part I enjoy this sharpened perception.

And how about lingering positive side effects?

Oh yeah.  I feel great.  Better than I have in years.  I am strong, my immune system is in balance and perhaps more vigorous than it had been previously.  I wake up every morning and sing a little song.  It goes something like this:  “I’m alive, I’m alive, I’m alive.”

What lifestyle changes has enrollment in this clinical trial entailed?

Well, obviously I commute to  MGH in Boston with greater frequency.  In the beginning, it was somewhat intense, but now I go once a month for PK’s (pharmacokinetics), a physical with Dr. Shaw and to pick up my drug supply.  I have spiral CT scans every two months.  I must obtain an ok for any new drug, prescription or over the counter, with the trial team before I take it.  Because of my slightly elevated liver enzymes, I avoid hard alcohol for the most part (occasional teeny martinis and wee margaritas), but still drink red wine in moderation.  It is necessary to record the time I take my drug each morning and evening as well as the time of the meal just prior.  This is certainly the most tedious part, and I am not always good at remembering.  Once or twice I have forgotten to take my dose of PF-02341066 as well.  Luckily, it has a rather long half life, and I have simply waited until the next dose (per my doctor’s recommendations).  And sadly, I can no longer eat grapefruit or drink grapefruit juice, as it interacts in a negative way with the drug.  Ending on a truly positive note; my ability to travel, exercise, and go about my daily life has in no way been restricted.  Although, when I broke my ankle Marguerite and Jose did tease me that there was a “no broken bones” clause in my clinical trial contract.

So is PF-02341066 really a miracle cure for cancer?

No.  It is not a cure.  Because I have a mutation of the EML4-ALK gene, my body would again manufacture cancerous cells if I were not taking an ALK inhibitor such as PF-02341066.  This is referred to as onco-addiction:  tumor cells are dependent on activated oncogenic signaling pathways, and the ALK inhibitor disrupts this process.

How long will it work for?

We are on a frontier here:  so the correct answer is that no one knows for sure. EGFR inhibitors have been effective for some individuals for several years and in some cases, longer.  However, it is not unlikely that eventually the cancer will “find a way around” these inhibitors.  The fact that I have had stable scans for 13 plus months is a good sign, and I have a gut feeling that the cancer will be held at bay for some time.

So what then?

I can only hope that PF-02341066 will continue to be effective for a long time, and that other drugs that target ALK (and other mutations, for those who are ALK negative) are in the pipeline.  In the meantime, I have been given the gift of more time, and each day is precious.  I also have the satisfaction of knowing that my enrollment in a clinical trial has in some way contributed to the search for more effective treatments for lung cancer, and, perhaps eventually, for some a cure.

The (positive) power of the media

L1010275At dusk the past two days, the moon has risen just over the lake, turning the water a shimmery silver.  When I have awakened in the middle of the night , it has been to a world transformed:  moonlight has bleached most everything a bluish white except for what it cannot reach, and that is in deep shadow.

This morning the ground was covered in hoar frost, and the lakes we passed on the way to Pete’s bus stop had the sluggish appearance of mercury.  Frosty vapor rose from the surface; it was simply exquisite.  When I returned home I grabbed my camera and snapped this shot of the leaves rimmed in frost.

Yesterday I drove to Boston for my trial date.  Everything except for the commute is now an abbreviated version of its former self.  My labs and my visit with Dr. Shaw take place in the thoracic oncology wing, and I visit infusion only to be dosed and to pick up a month’s worth of PF-02341066.  All of this is indicative of progress, but it also means less interaction with Marguerite, Sarah and Jose (and no Irene!).  I miss our more extended visits, but each brief reunion feels as if I am greeting dear friends–which is the direction in which these relationships have developed.

Alice still devotes as much time to our appointments as before; she is an extraordinary doctor in this regard.  Yesterday we reviewed the scans I had done almost two weeks hence.  I had been just a wee bit anxious, as it had been necessary to take a four day holiday from the drug, and I had not done that before.  My lungs looked great; everything is stable.  I am hugely relieved.

There is more good news.  ABC was in the house, filming a patient for a report that will air later in the week.  This gentleman had been watching television on June 2nd when the segment on personalized medicine was shown:  he is a young, never-smoker with advanced NSCLC that had not been responding to previous treatments.  Like me, he did not have the EGFR mutation.  When he heard my story and saw the image of my lungs, he was struck by the similarities to his own situation.  Although he lives some distance from Boston, he contacted Dr. Shaw and had his tumor tested for the ALK mutation.  The test was positive, and he started almost immediately on the PF-002341066 trial.  He too has had a fantastic response, and yesterday I had the pleasure of meeting him.  He looks fabulous and he said he feels great as well.

I have also been in close contact with another young, never-smoker who is enrolled in the Korean cohort of the trial.  She also was tested for the ALK-mutation after her sister saw the ABC report and contacted Dr. Shaw.  She too has had a very postive response.

This is all so exciting to me on several levels.  First, any good news from others in this battle is cause for celebration.  Secondly, to actually witness the positive impact of a newscast in which I was a participant.  All too often news is bad news, and we forget that media plays a very important role in the dissemination of information.  And it generally has a ripple effect:  after this new story airs on ABC World News, even more people will become aware of what could potentially be a life-saving treatment for them.

Finally, there is the even bigger picture.  Because I had (and a number of others as well) a positive response to PF-02341066 so early in the trial, there was always the possibility that it was a fluke.  As the trial continues, and a greater number of participants have positive responses, it is looking more like a trend.  I really believe that we are on the leading edge of some big breakthroughs in the study and treatment of lung cancer. November is Lung Cancer Awareness Month, and one of messages that advocates are trying to get across is the need for more funding to be earmarked for lung cancer research.  As one of a growing number of individuals who has personally benefitted from innovative research, I can testify to the validity of this call.  Let’s hope that the individuals and the organizations who can make this happen are listening.

Good news: Pfizer, Abbott and my latest scan

I headed down the highway to Boston at a little past six in the morning yesterday. Those grasses that I marveled at two days prior were now covered in dew, and in the early morning light it looked like so much pink froth.  Incredible!

Traffic is a bear this time of day, and even with my early departure, I arrived only a few minutes prior to my 9:30 a.m. appointment.  After the white ID bracelet was placed on my wrist, (hospital jewelry) my weight, blood pressure and oxygen levels were checked. I was then led to a room and given a warm blanket.  Rosalba did my blood draws. Jose provided me with a new schedule, a months supply of PF-02341066, and a hug. Irene stopped by for a chat and a wee bit of acupuncture, and Marguerite to check in and for conversation.  Dr. Shaw (Alice) gave me a brief physical and went over Monday’s scans. Happily, everything is stable.

When a radiologist reads a scan, they carefully note each nodule, micro calcification and appearance of inflammation.  My lungs have some of each. Although any of these features could indicate disease, they may also represent scarring and inflammation that is benign.  Stability, or a lack of visual change, is a very reassuring indication (surpassed only by the ever hoped for complete resolution).

As of October 1st, I will have been on the trial drug for one year.  A year of stability is huge.  I have stage IV NSCLC and I have gone for almost an entire year without progression of disease, AND I have felt great.  If you’re not jumping up and down yet, start now:  statistically speaking, I should probably be dead, and not only am I still alive, I am not sick.  I feel great.  This really is flipping amazing.

Yesterday the New York Times had an article about Pfizer’s current focus on developing new drugs to treat cancer (click here). Pfizer is the largest pharmaceutical company in the world, and in the past oncology has not been one of their top focuses. They are also the maker of the experimental drug (PF-02341066) that is responsible for the halt of my lung cancer.

This article comes on the heels of an announcement that Pfizer will collaborate with Abbott Laboratories to develop a test to identify genetic mutations in NSLC (click here). Abbott’s test shall be specifically designed to search for the ALK mutation present in approximately 6-7% of tumors, in order to determine who will best benefit from treatment with PF-02341066.

It is clear that both Pfizer and Abbott see great promise in targeted therapies and are prepared to pour a lot of time and money into research and development.  I couldn’t be happier. It’s good to have some very big guns up at the front in the war against cancer.  It’s a real morale booster for those of us in the trenches.

The “Now you see it, now you don’t” scan

Before I move on, I thought we’d take one last, long view of the before and after CT scans of my lungs. The scan on top was taken on September 16th of 2008 two weeks prior to starting the PF-02341066 trial. The lower scan was taken seven weeks after my lead-in dose (taken one week before starting regular doses) on November 19th.

beforeandafterlinneacancerslice1beforeandafterlinneacancerslice2 I had been receiving scans every three months for three years at the time of the September 2008 scan.  They had gone from questionable to progressively worse. “Interval increase in size and number of multiple bilateral pulmonary nodules is consistent with progression of metastatic disease”, read a report from August of 2007.

In stark contrast, the radiology report from November 19th of 2008 read: “Marked interval improvement of bilateral pulmonary lesions, with near complete resolution.  Small remaining lesions, left lower lung septal thickening, and left pleural effusion as above.”

I should point out that radiologist’s reports are, by necessity, very conservative in their wording.  Keeping this in mind, “near complete resolution” practically gushed with enthusiasm.

The scan from September illustrates clearly how far the cancer had advanced. The remaining upper lobe of my left lung was literally clouded with malignant nodules.  My right lung also shows a diffuse haziness indicating the spread of disease.  I had once again developed a hacking cough and increasing shortness of breath, and it was no longer possible to engage in many of the activities I had previously.  I was losing ground in my battle with cancer and it seemed inevitable that I would have to concede defeat.

But that was before PF-02341066.  Now I could literally and figuratively breathe again.  I was yet at war, but at long last I had a victory.

PF-02341066 trial moving to Phase III

David, Peter and I drove to Boston early this morning for my routine trial appointment. The trial team has decided that I only need to come to the hospital once a month now.   My scan regimen has changed slightly as well. Although I must still have scans every two months, it won’t be necessary to get the abdominal scan each time. That means no more barium milkshakes for the moment. YES for small victories.   My oncologist, Dr. Shaw, just returned from the 13th WCLC (World Conference on Lung Cancer) in San Francisco this past weekend. At the meeting, Dr. Shaw presented updated data on the efficacy of the PF-02341066 trial. The results continue to be very promising and continue to generate excitement in the field of thoracic oncology.
The trial will soon enter Phase III. Prior to FDA approval of a drug, a controlled and randomized trial must be conducted.  It will be at multiple locations around the globe and will enroll many more people.  All those enrolling in Phase III must have the ALK mutation as well as only one failed first line therapy.  The fact that it is randomized means that some subjects will receive standardized chemo rather than the trial drug. However, should they suffer adverse effects from the standard chemo, or have progression of disease at their first scan at six weeks, they will be permitted to switch to the trial drug.  A phase II of the trial will be running simultaneously (the primary goal of Phase I is to assess for safety and dose escalation, Phase II is efficacy of the drug). Those subjects who possess the ALK mutation, but have also had more than one failed first line therapy, may enroll in a Phase II of the trial. So–bottom line–you need to have the mutation.

It was also fun to see images of my CT scans that were used as slides at the presentation. She also showed us a chart of subject response and it was interesting to see the hard data. Although my own response was characterized by my oncologist and the radiologist as “an almost total response”, statistically it is approx. a 70%  PR, or partial response.

It is beyond me how they determine such things (although Dr. Shaw explained that the methodology is to assess a two dimensional shrinkage of tumor as shown by scans). My CT scan could hardly look much better. However, I know that we are continuing to watch an area that represents either scarring or lung cancer. Only the statistical percentage is surprising, and I learned early in this journey to not pay too much attention to numbers. I just know how good I feel and that I continue to wake up every morning.  Wasn’t it Woody Allen who said that “80% of success is showing up”?
We also talked more about how the trial drug actually works.  The mutation that I have acquired (it is not inherited and so has been caused by exposure to one or more carcinogens) means that my DNA has been permanently altered, and altered in such a way that it makes cancerous cells.  The altered gene has become an oncogene:  a gene that contributes to the conversion of a normal cell into a cancerous one.  By locating where that mutation was (on the ALK gene), researchers were able to pinpoint a target.  The trial drug (PF-02341066) is a targeted therapy.   It is referred to as cancer growth blocker.  Growth factors trigger the cancer cells to divide and grow, and cancer cells are often very sensitive to them.  If these growth factors can be blocked, it is possible to stop growth and division of the cancer cells.

PF-02341066 is a Tyrosine kinase inhibitor.  This refers to the type of chemical that it blocks:  in this case, enzymes called tyrosine kinases.  These enzymes attach to a receptor on a cancerous cell and signal it to divide.  The Tyroisne kinase inhibitor stops that signal.  In layman’s terms:  my cancer has not been cured.  It has been stalled, the growth and division of cancerous cells halted, possibly indefinitely.

Realistically, it is unknown how long this drug will be effective for.  When and if it stops working, the cancer will begin to grow again.  I hope for two things: that the cancer will be held at bay for a long time, and that in the meantime, other treatments are developed.  This is the way it is with cancer.  We, all of us with cancer, are truly at the frontier.  There is so much yet to discover, and I am so grateful to those who are dedicating their life work to this end. My very existence depends on it.